The goal of this project is an anatomical analysis of axon collateralization in the monoamine neuron systems. In the past decade brain systems have been identified according to neurotransmitter and the most extensively studied system are the monoamines, including the norepinephrine, dopamine and serotonin neuron systems. Our previous work has elucidated the detailed anatomical, biochemical and histochemical distribution of these neuron projections to the basal forebrain, cortex and neostriatum in the most widely used animal model, the rat. Each system is characterized by different qualities of the projection, including localization, density topography, laterality and axonal arborization of the axons. One important feature of these axons systems which has not been studied is the degree of axon collateralization to different nuclei in the brain. The degree of collateralization may provide economy and redundancy within the central nervous system and may form an important basis for the varied functional morphology evident in the norepinephrine, dopamine and serotonin systems. The new double labeling retrograde transport techniques with horseradish peroxidase, labeled wheat germ agglutenin and fluorescent compounds have provided a means for determining if neurons project to one, or more, nuclei in the brain. The experiments outlined in this grant proposal utilize these double labeling techniques to demonstrate the degree of axonal collateralization from monoamine neurons in the locus coeruleus, substantia nigra-ventral tegmental area and midbrain raphe to the telencephalon, diencephalon, cerebellum, medulla and spinal cord in the rat. An index of collaterlization is derived such that quantitative comparisons can be made between monoamine and other well defined neurotransmitter systems. These comparisons of collateralization will aid in distinguishing the unique participation of different brain systems in affective, sensory and motor disorders in the human patient.